Search results for "Deletions"
showing 10 items of 13 documents
Evolving by deleting: patterns of molecular evolution of Apple stem pitting virus isolates from Poland
2019
In this study, 267 coat protein gene (CP) sequences from 48 Polish isolates of Apple stem pitting virus (ASPV) were determined. The genetic structure of the virus population was analysed and possible mechanisms of molecular evolution explored. We found evidence of recombination within the ASPV population and the presence of 17 ASPV molecular variants that differ in the length, number and arrangement of deletions in the CP. Population genetic analyses showed significant variation among isolates from pear and apple trees, between isolates from the same host species and, more interestingly, within isolates, supporting the existence of significant levels of variability within individual hosts, …
9q33.3q34.11 microdeletion: new contiguous gene syndrome encompassing STXBP1, LMX1B and ENG genes assessed using reverse phenotyping
2016
International audience; The increasing use of array-CGH in malformation syndromes with intellectual disability could lead to the description of new contiguous gene syndrome by the analysis of the gene content of the microdeletion and reverse phenotyping. Thanks to a national and international call for collaboration by Achropuce and Decipher, we recruited four patients carrying de novo overlapping deletions of chromosome 9q33.3q34.11, including the STXBP1, the LMX1B and the ENG genes. We restrained the selection to these three genes because the effects of their haploinsufficency are well described in the literature and easily recognizable clinically. All deletions were detected by array-CGH …
Genetic Polymorphism in Wine Yeasts: Mechanisms and Methods for Its Detection
2017
The processes of yeast selection for using as wine fermentation starters have revealed a great phenotypic diversity both at interspecific and intraspecific level, which is explained by a corresponding genetic variation among different yeast isolates. Thus, the mechanisms involved in promoting these genetic changes are the main engine generating yeast biodiversity. Currently, an important task to understand biodiversity, population structure and evolutionary history of wine yeasts is the study of the molecular mechanisms involved in yeast adaptation to wine fermentation, and on remodeling the genomic features of wine yeast, unconsciously selected since the advent of winemaking. Moreover, the…
Whole Exome Sequencing Is the Preferred Strategy to Identify the Genetic Defect in Patients With a Probable or Possible Mitochondrial Cause
2018
Mitochondrial disorders, characterized by clinical symptoms and/or OXPHOS deficiencies, are caused by pathogenic variants in mitochondrial genes. However, pathogenic variants in some of these genes can lead to clinical manifestations which overlap with other neuromuscular diseases, which can be caused by pathogenic variants in non-mitochondrial genes as well. Mitochondrial pathogenic variants can be found in the mitochondrial DNA (mtDNA) or in any of the 1,500 nuclear genes with a mitochondrial function. We have performed a two-step next-generation sequencing approach in a cohort of 117 patients, mostly children, in whom a mitochondrial disease-cause could likely or possibly explain the phe…
Identification of control targets in Boolean molecular network models via computational algebra
2015
Motivation: Many problems in biomedicine and other areas of the life sciences can be characterized as control problems, with the goal of finding strategies to change a disease or otherwise undesirable state of a biological system into another, more desirable, state through an intervention, such as a drug or other therapeutic treatment. The identification of such strategies is typically based on a mathematical model of the process to be altered through targeted control inputs. This paper focuses on processes at the molecular level that determine the state of an individual cell, involving signaling or gene regulation. The mathematical model type considered is that of Boolean networks. The pot…
The severe phenotype of Diamond-Blackfan anemia is modulated by heat shock protein 70.
2017
International audience; Diamond-Blackfan anemia (DBA) is a rare congenital bone marrow failure syndrome that exhibits an erythroid-specific phenotype. In at least 70% of cases, DBA is related to a haploinsufficient germ line mutation in a ribosomal protein (RP) gene. Additional cases have been associated with mutations in GATA1. We have previously established that the RPL11+/Mut phenotype is more severe than RPS19+/Mut phenotype because of delayed erythroid differentiation and increased apoptosis of RPL11+/Mut erythroid progenitors. The HSP70 protein is known to protect GATA1, the major erythroid transcription factor, from caspase-3 mediated cleavage during normal erythroid differentiation.…
Type IV Laryngotracheoesophageal Cleft Associated with Type III Esophageal Atresia in 1p36 Deletions Containing the RERE Gene: Is There a Causal Role…
2018
The causes of embryological developmental anomalies leading to laryngotracheoesophageal clefts (LTECs) are not known, but are proposed to be multifactorial, including genetic and environmental factors. Haploinsufficiency of the RERE gene might contribute to different phenotypes seen in individuals with 1p36 deletions. We describe a neonate of an obese mother, diagnosed with type IV LTEC and type III esophageal atresia (EA), in which a 1p36 deletion including the RERE gene was detected. On the second day of life, a right thoracotomy and extrapleural esophagus atresia repair were attempted. One week later, a right cervical approach was performed to separate the cervical esophagus from the tra…
Manipulating mtDNA in vivo reprograms metabolism via novel response mechanisms.
2019
Mitochondria have been increasingly recognized as a central regulatory nexus for multiple metabolic pathways, in addition to ATP production via oxidative phosphorylation (OXPHOS). Here we show that inducing mitochondrial DNA (mtDNA) stress in Drosophila using a mitochondrially-targeted Type I restriction endonuclease (mtEcoBI) results in unexpected metabolic reprogramming in adult flies, distinct from effects on OXPHOS. Carbohydrate utilization was repressed, with catabolism shifted towards lipid oxidation, accompanied by elevated serine synthesis. Cleavage and translocation, the two modes of mtEcoBI action, repressed carbohydrate rmetabolism via two different mechanisms. DNA cleavage activ…
A ceRNA approach may unveil unexpected contributors to deletion syndromes, the model of 5q- syndrome.
2015
In genomic deletions, gene haploinsufficiency might directly configure a specific disease phenotype. Nevertheless, in some cases no functional association can be identified between haploinsufficient genes and the deletion-associated phenotype. Transcripts can act as microRNA sponges. The reduction of transcripts from the hemizygous region may increase the availability of specific microRNAs, which in turn may exert in-trans regulation of target genes outside the deleted region, eventually contributing to the phenotype. Here we prospect a competing endogenous RNA (ceRNA) approach for the identification of candidate genes target of epigenetic regulation in deletion syndromes. As a model, we an…
Mutation analysis of the SPG4 gene in Italian patients with pure and complicated forms of spastic paraplegia
2010
Mutations in the SPG4 gene are the most common causes of hereditary spastic paraplegia (HSP) accounting for up to 40% of autosomal dominant (AD) forms and 12-18% of sporadic cases. The phenotype associated with HSP due to mutations in the SPG4 gene tends to be pure. There is increasing evidence, however, of patients with complicated forms of spastic paraplegia in which SPG4 mutations were identified. A cohort of 38 unrelated Italian patients with spastic paraplegia, of which 24 had a clear dominant inheritance and 14 were apparently sporadic, were screened for mutations in the SPG4 gene.We identified 11 different mutations, six of which were novel (p.Glu143GlyfsX8, p.Tyr415X, p.Asp548Asn, c…